Effect of chromatin structure on quantitative ultrasound parameters
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Maurice Pasternak1,5, Lilian Doss1,2, Golnaz Farhat1,2,3, Azza Al-Mahrouki1,2, Christina Hyunjung Kim1,2, Michael Kolios5, William Tyler Tran1,4, Gregory J. Czarnota1,2,3,4
1Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Canada
2Physical Sciences, Sunnybrook Research Institute, Toronto, Canada
3Department of Medical Biophysics, University of Toronto, Toronto, Canada
4Department of Radiation Oncology, University of Toronto, Toronto, Canada
5Department of Physics, Ryerson University, Toronto, Canada
Gregory J. Czarnota, email: [email protected]
Keywords: ultrasound, chromatin, spectral analysis, form-factor analysis, electron microscopy
Received: September 14, 2016 Accepted: November 22, 2016 Published: January 25, 2017
High-frequency ultrasound (~20 MHz) techniques were investigated using in vitro and ex vivo models to determine whether alterations in chromatin structure are responsible for ultrasound backscatter changes in biological samples. Acute myeloid leukemia (AML) cells and their isolated nuclei were exposed to various chromatin altering treatments. These included 10 different ionic environments, DNA cleaving and unfolding agents, as well as DNA condensing agents. Raw radiofrequency (RF) data was used to generate quantitative ultrasound parameters from spectral and form factor analyses. Chromatin structure was evaluated using electron microscopy. Results indicated that trends in quantitative ultrasound parameters mirrored trends in biophysical chromatin structure parameters. In general, higher ordered states of chromatin compaction resulted in increases to ultrasound paramaters of midband fit, spectral intercept, and estimated scatterer concentration, while samples with decondensed forms of chromatin followed an opposite trend. Experiments with isolated nuclei demonstrated that chromatin changes alone were sufficient to account for these observations. Experiments with ex vivo samples indicated similar effects of chromatin structure changes. The results obtained in this research provide a mechanistic explanation for ultrasound investigations studying scattering from cells and tissues undergoing biological processes affecting chromatin.
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